Biomedical subjects

J Dietrich

Publications and source records attributed to J Dietrich.

At least 19 recordsLinked to original sources

PubMed2006

[Presenting problem: abdominal pain].

The Saxon Study for General Medicine (SESAM) investigated the reasons why patients consulted the general physician, what diagnoses were established, and how the patients were subsequently treated. In the majority of cases, the reason for the abdominal complaints was located in the gastrointestinal or urogenital tract, in the presence of infections or psychosomatic problems. Gynecological problems must also be considered, while diseases other than gastrointestinal are of no significance for the differential diagnosis of abdominal complaints in the general physician's office.

Abdominal Pain↗

PubMed2005

A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures.

Inner-city minority populations are high-risk groups for adverse birth outcomes and also more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia Center for Children's Environmental Health (CCCEH) is conducting a prospective cohort study of 700 northern Manhattan pregnant women and newborns to examine the effects of prenatal exposure to these common toxicants on fetal growth, early neurodevelopment, and respiratory health. This paper summarizes results of three published studies demonstrating the effects of prenatal ETS, PAH, and pesticides on birth outcomes and/or neurocognitive development [Perera FP, Rauh V, Whyatt RM, Tsai WY, Bernert JT, Tu YH, et al. Molecular evidence of an interaction between prenatal environment exposures on birth outcomes in a multiethnic population. Environ Health Perspect 2004;12:630-62; Rauh VA, Whyatt RM, Garfinkel R, Andrews H, Hoepner L, Reyes A, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol 2004;26:373-85; Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, et al. Prenatal insecticide exposures, birth weight and length among an urban minority cohort. Environ Health Perspect, in press]. To evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides, researchers analyzed questionnaire data, cord blood plasma (including biomarkers of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of PAHs). Self-reported ETS was associated with decreased head circumference (P = 0.04), and there was a significant interaction between ETS and adducts such that combined exposure had a significant multiplicative effect on birth weight (P = 0.04) and head circumference (P = 0.01) after adjusting for confounders. A second analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum material hardship (unmet basic needs in the areas of food, housing, and clothing) on 2-year cognitive development. Both exposures depressed cognitive development (P < 0.05), and there was a significant interaction such that children with exposure to both ETS and material hardship exhibited the greatest cognitive deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were inversely associated with birth weight and/or length (P < 0.05). These results underscore the importance of policies that reduce exposure to ETS, air pollution, and pesticides with potentially adverse effects on fetal growth and child neurodevelopment.

Child↗

PubMed2004

Third ventriculostomy in communicating hydrocephalus in adult patients -- the role of lumbar and cranial cerebrospinal fluid outflow measurement.

OBJECTIVE: To evaluate the value of CSF outflow resistance testing as a criterion for endscopic treatment in case of communicating hydrocephalus. METHODS: 12 patients with communicating hydrocephalus were integrated in a prospective study from 1999 - 2001. Under the assumption of different hydromechanical properties of both spinal and cerebral CSF compartment the resorption capacity was measured. V.-p. shunting, ventriculostomy or conservative treatment were performed dependent on the results and clinical outcome was evaluated. RESULTS: Six patients with pathological lumbar testing underwent primary ventriculo-peritoneal shunting. In 6 of the 12 cases the lumbar CSF resorption capacity was found to be normal and cerebral testing was accomplished. Two patients with normal spinal and cerebral resorption capacity were not operated. In the remaining 4 patients cerebral testing was found to be pathological and ventriculostomy was performed. An improvement of clinical symptoms was observed in patients operated with a v.-p. shunt and in the VCS group as well. CONCLUSIONS: This study demonstrates that there is a subgroup of patients with morphological communicating hydrocephalus that is characterized by a functional dissociation of hydromechanical properties of intracranial and spinal CSF compartment. In cases of regular CSF resorption but restricted CSF outflow from the ventricular system to the subarachnoid space ventriculo-peritoneal shunting may be an efficient therapy, but VCS was proved to be an efficient alternative.

Aged↗

PubMed2002

[Cerebral MRI and evoked potentials in Wilson disease. Comparison of findings in patients with neurological follow-up].

Wilson's disease is caused by toxic copper accumulation, which leads predominantly to hepatic and basal ganglia damage. Characteristic findings in MRI and electrophysiologic examinations are described according to the occurrence of neurological symptoms. In the present study, 28 patients suffering from Wilson's disease (neurological type) were investigated. The results of MRI are compared with abnormalities of evoked potentials (BAEP, MSEP, T-VEP, MEP). All patients show hypodensities in the basal ganglial area (putamen and GI. pallidus) regularly combined with atrophy of the cerebrum and cerebellum in MRI. Signal abnormalities in the mesencephalic region (46% occurrence) and Nc. dentatus (36% occurrence) are combined with the other findings in variable patterns. Only slight changes are found in the pontine region. BAEP are disturbed in 71% of all cases and MSEP in 46%. Combined abnormalities of BAEP and MSEP were found in 39%. Pathological values occurred with a lower frequency in T-VEP (36%) and MEP (39%). The comparison of MRI findings with electrophysiological data done separately for each patient reveals no strong correlation between both methods. Individual MRI findings do not correspond with the patterns of disturbed evoked potentials and vice versa. Therefore we conclude that these methods, MRI and electrophysiological evaluation, supplement each other. Magnetic resonance imaging and electrophysiological evaluation should be performed simultaneously for therapy monitoring.

Adult↗

PubMed2002

[Early clinical management after polytrauma with 1 and 4 slice spiral CT].

In the early clinical phase the comprehensive imaging of patients with multiple trauma using helical CT is already established. Aim of this study was to assess whether MSCT may improve the patient management and the diagnostic results. The procedure is designed as follows: after life-thretening treatment x-ray of chest and ultrasound are carried out in the emergency room. Then the patient is moved to CT. From 1998 to december 2000 241 patients were examined using a single slice helical CT (Somatom plus 4), in 2001 79 patients using a 4-slice helical CT (Somatom VZ, Siemens Med.Sol.). After CT selected radiograms of the extremities were taken. 359 of 360 procedures were carried out successfully. Excluding 1 case (death during 1-sl.h CT) all relevant lesions of head, neck, and body were diagnosed. Although the patients had an injury severity score of approximately 30. The change from 1 slice-helical CT to 4 slice-helical CT allowed us to reduce the stay in the CT room from 28 to 16 min. The total lethality decreased by approximately 4%. Advantages for the patient arose from the standardized examination protocol using multislice CT. If integrated in an interdisciplinary management concept, it is a good compromise between examination time, comprehensive diagnostic imaging, life-saving therapeutic procedures, and therapy planning.

Efficiency, Organizational↗

PubMed2002

In vitro production and characterization of partly assembled human CD3 complexes.

Pairwise assembly of human CD3 chains takes place in the endoplasmic reticulum of T cells. Subsequently, the CD3 heterodimers form complexes with Ti alpha and Tiss chains forming hexameric Ti alpha beta CD3 gamma epsilon delta epsilon complexes. Finally, association with the zeta 2 homodimer occurs in Golgi apparatus before the fully assembled T-cell receptor is transported to the cell surface. To study the structural properties of the human CD3 chains, we have developed new methods to produce and fold the extracellular domains of CD3 gamma, CD3 delta and CD3 epsilon. Proteins were expressed in Escherichia coli as denatured chains and de novo folded in vitro. CD3 gamma and CD3 epsilon folded as soluble monomers, whereas CD3 delta did not yield any soluble proteins. When folding the chains pairwise, soluble CD3 gamma epsilon and CD3 delta epsilon heterodimers could be isolated, whereas CD3 gamma delta heterodimers were not produced. Using antibodies as structural probes, we identified two different types of antigenic epitopes that were dependent on heterodimerization. Our data indicate that CD3 epsilon undergoes a conformational change after dimerization with CD3 gamma or CD3 delta. Furthermore, we demonstrated that the CD3 gamma epsilon heterodimer could be purified using immunoaffinity chromatography.

Antibodies, Monoclonal↗

PubMed2002

Pictorial review: Colour Doppler ultrasound flow patterns in the portal venous system.

Doppler ultrasound is a well established method for assessment of the portal venous system to detect the direction of portal blood flow. It is helpful for non-invasive diagnosis of intra-abdominal portosystemic shunts, especially in patients with cirrhosis. Less attention has been paid to other influences on portal venous flow, e.g. tricuspid regurgitation, increased hepatic out-flow resistance, respiratory cycle. The aim of this pictorial review is to describe the spectrum of physiological and pathological Doppler ultrasound flow patterns in the portal venous system.

Adult↗

PubMed2001

Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin.

BACKGROUND: Resistance to chemotherapeutic agents and poor blood-brain barrier penetration are major limitations in the treatment of malignant glioma. To improve drug delivery across the blood-brain barrier, the authors used doxorubicin as liposomal encapsulated formulation (Caelyx, Scheringh-Plough, Munich, Germany) in therapy of recurrent malignant glioma. METHODS: Fifteen patients with recurrent high-grade gliomas were included in the study. Of these, 13 patients could be evaluated, including 6 patients with glioblastoma, 1 patient with gliosarcoma and 6 patients with anaplastic astrocytoma. The treatment consisted of liposomal doxorubicin (20 mg/m(2)), applied intravenously every 2 weeks. RESULTS: Stabilization of the disease was observed in 54% (7 of 13) of patients. Partial response and complete response (CR) were not observed. Median time-to-progression was 11 weeks. Progression free survival at 12 months was 15%. Median overall survival (OS) after doxorubicin therapy was 40.0 weeks, whereas the median OS after diagnosis reached 20.0 months (87.0 weeks). Doxorubicin was well tolerated, with main side effects being palmoplantar erythrodysesthesia occurring in 38% and myelotoxicity (World Health Organization Grade 3-4) in 31% of the patients. CONCLUSIONS: Doxorubicin has been shown to be a safe treatment with moderate activity that may lead to long-term stabilization in recurrent high-grade glioma patients. Of note, median OS after all and after initiation of recurrence therapy was prolonged in comparison with the OS in other Phase II studies, as recently described by Wong et al. (Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999;17:2572.).

Adult↗

PubMed2001

The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain.

T cell receptor (TCR)-interacting molecule (TRIM) is a recently identified transmembrane adaptor protein, which is exclusively expressed in T cells. Here we demonstrate that in mature T cells, TRIM preferentially interacts with the TCR via the TCR-zeta chains and to a lesser extent via the CD3-straightepsilon/gamma heterodimer. Transient or stable overexpression of TRIM in Jurkat T cells results in enhancement of TCR expression on the cell surface and elevated induction of Ca(2+) mobilization after T cell activation. TRIM-mediated upregulation of TCR expression results from inhibition of spontaneous TCR internalization and stabilization of TCR complexes on the cell surface. Collectively, our data identify TRIM as a novel integral component of the TCR complex and suggest that one function of TRIM might be to modulate the strength of signals transduced through the TCR through regulation of TCR expression on the cell surface.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Large scale expression, purification and 2D crystallization of recombinant plant plasma membrane H+-ATPase.

P-type ATPases convert chemical energy into electrochemical gradients that are used to energize secondary active transport. Analysis of the structure and function of P-type ATPases has been limited by the lack of active recombinant ATPases in quantities suitable for crystallographic studies aiming at solving their three-dimensional structure. We have expressed Arabidopsis thaliana plasma membrane H+-ATPase isoform AHA2, equipped with a His(6)-tag, in the yeast Saccharomyces cerevisiae. The H+-ATPase could be purified both in the presence and in the absence of regulatory 14-3-3 protein depending on the presence of the diterpene fusicoccin which specifically induces formation of the H+-ATPase/14-3-3 protein complex. Amino acid analysis of the purified complex suggested a stoichiometry of two 14-3-3 proteins per H+-ATPase polypeptide. The purified H(+)-ATPase readily formed two-dimensional crystals following reconstitution into lipid vesicles. Electron cryo-microscopy of the crystals yielded a projection map at approximately 8 A resolution, the p22(1)2(1) symmetry of which suggests a dimeric protein complex. Three distinct regions of density of approximately equal size are apparent and may reflect different domains in individual molecules of AHA2.

14-3-3 Proteins↗

PubMed2001

Two-dimensional crystallization of a membrane protein on a detergent-resistant lipid monolayer.

Two-dimensional crystals of a membrane protein, the proton ATPase from plant plasma membranes, have been obtained by a new strategy based on the use of functionalized, fluorinated lipids spread at the air-water interface. Monolayers of the fluorinated lipids are stable even in the presence of high concentrations of various detergents as was established by ellipsometry measurements. A nickel functionalized fluorinated lipid was spread into a monolayer at the air-water interface. The overexpressed His-tagged ATPase solubilized by detergents was added to the subphase. 2D crystals of the membrane protein, embedded in a lipid bilayer, formed as the detergent was removed by adsorption. Electron microscopy indicated that the 2D crystals were single layers with dimensions of 10 microm or more. Image processing yielded a projection map at 9 A resolution, showing three well-separated domains of the membrane-embedded proton ATPase.

Adsorption↗

PubMed2001

Syntheses and structural characterization of dinuclear and tetranuclear iron(III) complexes with dinucleating ligands and their reactions with hydrogen peroxide.

The iron(III) complexes [Fe(2)(HPTB)(mu-OH)(NO(3))(2)](NO(3))(2).CH(3)OH.2H(2)O (1), [Fe(2)(HPTB)(mu-OCH(3))(NO(3))(2)](NO(3))(2).4.5CH(3)OH (2), [Fe(2)(HPTB)(mu-OH)(OBz)(2)](ClO(4))(2).4.5H(2)O (3), [Fe(2)(N-EtOH-HPTB)(mu-OH)(NO(3))(2)](ClO(4))(NO(3)).3CH(3)OH.1.5H(2)O (4), [Fe(2)(5,6-Me(2)-HPTB)(mu-OH)(NO(3))(2)](ClO(4))(NO(3)).3.5CH(3)OH.C(2)H(5)OC(2)H(5).0.5H(2)O (5), and [Fe(4)(HPTB)(2)(mu-F)(2)(OH)(4)](ClO(4))(4).CH(3)CN.C(2)H(5)OC(2)H(5).H(2)O (6) were synthesized (HPTB = N,N,N',N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane, N-EtOH-HPTB = N,N,N',N'-tetrakis(N' '-(2-hydroxoethyl)-2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane, 5,6-Me(2)-HPTB = N,N,N',N'-tetrakis(5,6-dimethyl-2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane). The molecular structures of 2-6 were established by single-crystal X-ray crystallography. Iron(II) complexes with ligands similar to the dinucleating ligands described herein have been used previously as model compounds for the dioxygen uptake at the active sites of non-heme iron enzymes. The same metastable (mu-peroxo)diiron(III) adducts were observed during these studies. They can be prepared by adding hydrogen peroxide to the iron(III) compounds 1-6. Using stopped-flow techniques these reactions were kinetically investigated in different solvents and a mechanism was postulated.

Crystallography, X-Ray↗

PubMed2001

Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) inhibits TCR signaling and actin cytoskeleton reorganization.

Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) is a receptor, specific for MHC class I molecules, that inhibits lymphoid and myeloid cells. Here, we analyzed the molecular and cellular mechanisms by which ILT2 modulates T cell activation in primary CTLs and transfected T cell lines. We found that cross-linking with the TCR and the activity of Src tyrosine kinase p56(lck) were required for phosphorylation of ILT2 and subsequent recruitment of Src homology protein 1. In contrast, ILT2 triggering resulted in reduced phosphorylation of TCRzeta and linker for activation of T cells, which led to reduced TCRzeta-ZAP70 complex formation, as well as extracellular signal-related kinase 1 and 2 activation. Furthermore, ILT2 inhibited both superantigen and anti-TCR Ab-induced rearrangement of the actin cytoskeleton. The inhibitory effect mediated by ILT2 is probably concentrated at the APC-T cell interface because both TCR and ILT2 were strongly polarized toward the APC upon engagement by their specific ligands. Thus, ILT2 inhibits both signaling and cellular events involved in the activation of T cells.

Actins↗

PubMed2001

Characterization of the maltooligosyl trehalose synthase from the thermophilic archaeon Sulfolobus acidocaldarius.

We report the molecular characterization and the detailed study of the recombinant maltooligosyl trehalose synthase mechanism from the thermoacidophilic archaeon Sulfolobus acidocaldarius. The mts gene encoding a maltooligosyl trehalose synthase was overexpressed in Escherichia coli using the T7-expression system. The purified recombinant enzyme exhibited optimum activity at 75 degrees C and pH 5 with citrate-phosphate buffer and retained 60% of residual activity after 72 h of incubation at 80 degrees C. The recombinant enzyme was active on maltooligosaccharides such as maltotriose, maltotetraose, maltopentaose and maltoheptaose. Investigation of the enzyme action on maltooligosaccharides has brought much insight into the reaction mechanism. Results obtained from thin-layer chromatography suggested a possible mechanism of action for maltooligosyl trehalose synthase: the enzyme, after converting the alpha-1,4-glucosidic linkage to an alpha-1,1-glucosidic linkage at the reducing end of maltooligosaccharide glc(n) is able to release glucose and maltooligosaccharide glc(n-1) residues. And then, the intramolecular transglycosylation and the hydrolytic reaction continue, with the maltooligosaccharide glc(n-1) until the initial maltooligosaccharide is reduced to maltose. An hypothetical mechanism of maltooligosyl trehalose synthase acting on maltooligosaccharide is proposed.

Amino Acid Sequence↗

PubMed2001

Transnasal and transsphenoidal MRI-guided biopsies of petroclival tumors.

Magnetic resonance imaging (MRI) allows excellent tissue characterization in the area of the petroclival region and can depict lesions not visualized with ultrasound or computed tomography (CT). The aim of this study was to demonstrate the clinical feasibility and utility of an interactive MR-guidance system to target and biopsy tumors in the petroclival region. MRI-guided biopsies of 10 patients with tumors in the clivus and petrous apex were performed in an open 0.5-T MR system. Lesions were targeted through a transsphenoidal or transnasal approach. Imaging during biopsies was achieved by a combination of standard and interactive mode. T1-weighted spin-echo, T2-weighted fast spin-echo (FSE), and three-dimensional T1-weighted gradient-echo (GRE) scans (standard mode) were selected to provide optimal tissue characterization for both the lesion and surrounding structures and varied according to the anatomic site. For interactive imaging, T1-weighted GRE and T2-weighted FSE sequences were used. We performed MRI-guided transsphenoidal biopsies in 10 patients who had lesions identified by CT (n = 5) and/or MRI (n = 10). The indications for biopsies were to differentiate between suspected malignant processes (n = 4 ) and benign processes (n = 6). Lesions adjacent to structures like the internal carotid artery were accurately targeted in particular. All biopsies were performed successfully and were the basis for selection of further treatment. No complications occurred during the procedures. An open MR system allows interactive control of biopsies in the area of the petroclival region, providing maximum patient safety and diagnostic accuracy not possible in other systems. The advantages of MRI tissue characterization are combined with an interactive, one-step method of localization and targeting, as well as tissue sampling. J. Magn. Reson. Imaging 2001;13:3-11.

Biopsy, Needle↗

PubMed2001

Rapidly growing tumor-like brain lesion.

Listeria monocytogenes accounts for 8-11% of the cases of bacterial meningitis which is associated with high mortality in patients with serious underlying diseases or those receiving immunosuppressive treatment. Brain abscess due to L. monocytogenes is a very rare occurrence. The case reported here concerns a 54-year-old female patient with a rapidly growing tumor-like brain lesion. L. monocytogenes type 4b could be cultured from blood and brain biopsy. Despite antimicrobial therapy with ampicillin and gentamicin, the patient died 11 days after admission to the hospital. The growing numbers of elderly and immunocompromised patients will increasingly confront physicians with patients with listeriosis. Delayed therapy in patients treated with corticosteroids may result in a fatal outcome.

Adrenal Cortex Hormones↗

PubMed2001

Characterization of two DNA polymerases from the hyperthermophilic euryarchaeon Pyrococcus abyssi.

The complete genome sequence of the hyperthermophilic archaeon Pyrococcus abyssi revealed the presence of a family B DNA polymerase (Pol I) and a family D DNA polymerase (Pol II). To extend our knowledge about euryarchaeal DNA polymerases, we cloned the genes encoding these two enzymes and expressed them in Escherichia coli. The DNA polymerases (Pol I and Pol II) were purified to homogeneity and characterized. Pol I had a molecular mass of approximately 90 kDa, as estimated by SDS/PAGE. The optimum pH and Mg(2+) concentration of Pol I were 8.5-9.0 and 3 mm, respectively. Pol II is composed of two subunits that are encoded by two genes arranged in tandem on the P. abyssi genome. We cloned these genes and purified the Pol II DNA polymerase from an E. coli strain coexpressing the cloned genes. The optimum pH and Mg(2+) concentration of Pol II were 6.5 and 15-20 mm, respectively. Both P. abyssi Pol I and Pol II have associated 3'-->5' exonuclease activity although the exonuclease motifs usually found in DNA polymerases are absent in the archaeal family D DNA polymerase sequences. Sequence analysis has revealed that the small subunit of family D DNA polymerase and the Mre11 nucleases belong to the calcineurin-like phosphoesterase superfamily and that residues involved in catalysis and metal coordination in the Mre11 nuclease three-dimensional structure are strictly conserved in both families. One hypothesis is that the phosphoesterase domain of the small subunit is responsible for the 3'-->5' exonuclease activity of family D DNA polymerase. These results increase our understanding of euryarchaeal DNA polymerases and are of importance to push forward the complete understanding of the DNA replication in P. abyssi.

Amino Acid Sequence↗

PubMed2001

T-cell receptor downregulation by ceramide-induced caspase activation and cleavage of the zeta chain.

Regulation of T-cell receptor (TCR) cell surface expression levels is probably an important mechanism by which T-cell responsiveness is controlled. Previously, two distinct pathways for TCR downregulation have been described. One is dependent on protein kinase C (PKC) and the leucine-based receptor-sorting motif (L-based motif) of the CD3 gamma chain but independent of tyrosine kinases, whereas the other is dependent on the tyrosine kinase activation but independent of the PKC and the CD3 gamma L-based motif. In this study, we describe a new pathway for TCR downregulation distinct from both the PKC/CD3 gamma L-based motif-dependent and the tyrosine kinase-dependent pathways. This pathway is dependent on ceramide-induced activation of caspases and correlate with caspase-mediated cleavage of the zeta chain. Thus, a 10--15% downregulation of the TCR was induced following the treatment of the T cells with ceramide for 4 h. A close correlation between TCR downregulation, caspase activation, and cleavage of the zeta chain was found. Furthermore, the caspase inhibitors abolished the cleavage of the zeta chain and TCR downregulation in parallel with the inhibition of the caspase activity.

Amino Acid Chloromethyl Ketones↗